EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome (ARGUS)

January 20, 2024 updated by: Epygenix

A 20-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children and Adult Participants With Dravet Syndrome (ARGUS Trial)

The purpose of this study is to evaluate the safety and efficacy of EPX-100 as adjunctive therapy in children and adult participants with Dravet Syndrome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EPX-100 as adjunctive therapy in children and adult participants with Dravet Syndrome. The study consists of a 4-week observational period, a 16-week double blind period and a 3-year open label extension.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lorianne Masuoka, M.D.
  • Phone Number: (415) 933-0826
  • Email: lm@epygenix.com

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • Recruiting
        • UBC Children's Hospital Research Institute
        • Principal Investigator:
          • Mary Connolly, MD
        • Contact:
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Recruiting
        • Children's Hospital of Eastern Ontario
        • Contact:
        • Principal Investigator:
          • Katherine Muir, MD, FRCPC
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • The Hospital for Sick Children
        • Contact:
        • Principal Investigator:
          • Elizabeth Donner, MD
        • Contact:
      • Toronto, Ontario, Canada, M5T 2S8
        • Recruiting
        • Toronto Western Hospital, University Health Network
        • Principal Investigator:
          • Danielle M Andrade, MD
        • Contact:
  • Georgia
      • Tbilisi, Georgia, 0160
        • Recruiting
        • LTD Medi Club Georgia LLC
        • Principal Investigator:
          • Gia Melikishvili, MD
        • Contact:
      • Tbilisi, Georgia, 0186
        • Recruiting
        • LTD Institute of Neurology and Neuropsychology
        • Principal Investigator:
          • David Kvernadze, MD
        • Contact:
      • Tbilisi, Georgia, 0159
        • Not yet recruiting
        • LEPL Tbilisi State Medical University, Givi Zhvania Academic, Clinic of Pediatry
        • Principal Investigator:
          • Sophia Bakhtadze, MD
        • Contact:
  • Hungary
      • Budapest, Hungary, 1083
        • Not yet recruiting
        • Semmelweis University First Department of Pediatrics, Division of Child Neurology
        • Principal Investigator:
          • Viktor Farkas, MD
        • Contact:
  • Spain
    • Catalonia
      • Barcelona, Catalonia, Spain, 08025
        • Recruiting
        • Hospital de La Santa Creu I Sant Pau
        • Contact:
        • Principal Investigator:
          • Susana Boronat, MD
    • Madrid Provincia
      • Madrid, Madrid Provincia, Spain, 28009
        • Not yet recruiting
        • Hospital Universitario Infantil Niño Jesus
        • Contact:
        • Principal Investigator:
          • Victor Soto, MD
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Terminated
        • Children's Hospital of Los Angeles
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Medical Center
        • Principal Investigator:
          • Ernesto Gonzalez-Giraldo, MD
        • Contact:
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Nemours Children's Hospital-DE
        • Contact:
        • Principal Investigator:
          • Stephen Falchek, MD
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Principal Investigator:
          • Linda C Laux, MD
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan- Mott Children's Hospital
        • Principal Investigator:
          • Julie Ziobro, MD, PhD
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Not yet recruiting
        • Children's Hospital & Medical Center
        • Contact:
        • Principal Investigator:
          • Sookyong Koh, MD, PhD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Terminated
        • Northeast Regional Epilepsy Group
    • New York
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Weill Cornell Medicine/New York-Presbyterian Hospital
        • Contact:
        • Principal Investigator:
          • Zachary Grinspan, MD. MS
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest Baptist Health Sciences Department of Neurology
        • Contact:
        • Principal Investigator:
          • Gautam Popli, MD, MBA
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital
        • Contact:
        • Principal Investigator:
          • Gewalin Aungaroon, MD
      • Cleveland, Ohio, United States, 44195
        • Not yet recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Elia Pestana Knight, MD
        • Contact:
      • Columbus, Ohio, United States, 43205
        • Not yet recruiting
        • Nationwide Children's Hospital
        • Principal Investigator:
          • Anup Patel, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Principal Investigator:
          • Eric Marsh, MD, PhD
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38103
        • Terminated
        • Le Bonheur Children's Hospital
    • Texas
      • Austin, Texas, United States, 78757
        • Recruiting
        • Child Neurology Consultants of Austin
        • Principal Investigator:
          • Karen Keough, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University of Utah
        • Contact:
        • Principal Investigator:
          • Angela Peters, MD
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's
        • Principal Investigator:
          • Russell P Saneto, DO, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male and female participants 2 years and older at time of consent.
  2. Participant or parent/Legally Authorized Representative (LAR) willing and able to provide written informed consent, assent (if applicable) prior to initiation of any study related procedures.

  3. Clinical diagnosis of Dravet Syndrome. Participants must have seizures which are not completely controlled by AEDs with the following criteria:

    • Onset of seizures prior to 18 months of age,
    • Normal development at onset,
    • History of seizures that are generalized, unilateral clonic, and/or hemiclonic,
    • Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of Dravet Syndrome), and
    • Genetic mutation of the SCN1A gene must be documented.
  4. The participant must be approved to participate by the Independent Reviewer, in collaboration with the PI. Participants will be approved for participation following review of the participant's medical and seizure history, historical neuroimaging, historical EEGs, genetic report confirming SCN1A mutation, and review and classification of at least 28 days of baseline seizures.
  5. ≥4 countable convulsive seizures within minimum 28-day screening/baseline period (e.g., hemiclonic, secondarily generalized tonic-clonic, generalized tonic-clonic, tonic, clonic, tonic/atonic (resulting in a drop), and focal with clear observable motor signs).
  6. Participants should be on a stable regimen of AEDs ≥30 days prior to Visit 1 and generally in good health.
  7. Participant or parent/ LAR is able and willing to maintain an accurate and complete daily seizure and medication diary for the duration of the trial.
  8. Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative serum or urine pregnancy test at the screening (Visit 1) and Randomization (Visit 2). A WCBP is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months, surgical sterilization, or adequate barrier methods (e.g., diaphragm and foam). Use of oral contraceptives in combination with another method (e.g., a spermicidal cream) is acceptable. In participants who are not sexually active, abstinence is an acceptable form of birth control and urine will be tested per protocol. Women who are of non-child-bearing potential, i.e., post-menopause, must have this condition captured in their medical history. Pregnant women are excluded from this study.

Exclusion Criteria:

The presence of any of the following excludes a participant from study enrollment:

  1. Known sensitivity, allergy, or previous exposure to EPX-100 (clemizole HCl).
  2. Exposure to any investigational drug or device <90 days prior to screening or plans to participate in another drug or device trial at any time during the study.
  3. Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease.
  4. Concurrent use of drugs known to interfere with EPX-100, including moderate or severe inducers or inhibitors of CYP3A4/5/7. Specifically, concurrent use of carbamazepine, oxcarbazepine and/or phenytoin, as well as refraining from grapefruits and grapefruit juice during the study period. Refer to Appendix 1 for a list of prohibited drugs.
  5. Prior or concurrent use of lorcaserin.

  6. Concurrent use of fenfluramine. Participants with prior use of fenfluramine within the previous 3 months, or without proper documentation of an echocardiogram, at minimum 3 months following the last dose of fenfluramine, to ensure that the participant does not meet any criteria for drug-related (fenfluramine) cardiac valvular heart disease and/or drug-related pulmonary arterial hypertension (PAH) as indicated by any of the following:

    • documented mild or greater aortic regurgitation [AR] or moderate or greater mitral regurgitation [MR]
    • significant (greater than mild) tricuspid regurgitation
    • abnormally thickened cardiac valve and/or has restricted motion of the valve leaflets
    • elevated right heart/pulmonary artery pressure >35mmHg
  7. Has any medical condition that, in the PI's judgment, is considered to be clinically significant and could potentially affect participant safety or study outcome, including but not limited to: clinically significant cardiac disease (including angina, congestive heart failure, uncontrolled hypertension, and history of arrhythmias), renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism, or excretion of drugs.
  8. Has an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 3 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active arm with EPX-100 (Clemizole HCl)
EPX-100 oral solution
Drug: EPX-100 (Clemizole HCl)
Daily dose of EPX100
Other Names:
  • Clemizole
  • Clemizole Hydrochloride
  • Clemizole HCl
Placebo Comparator: Placebo arm
Color- and taste-matched placebo oral solution dosed to match the active arm.
Drug: Placebo
Daily dose of Placebo
Other Names:
  • Placebo to match EPX-100 solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline.
Time Frame: 20 weeks
The mean percent change in countable convulsive seizure frequency (CCSF1) in the Titration and Maintenance (T+M) periods relative to baseline.
20 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The difference between EPX-100 vs placebo in the number of countable convulsive seizure-free days in the T+M periods relative to baseline.
Time Frame: 20 weeks
The difference between EPX-100 vs placebo in the number of countable convulsive seizure-free days in the T+M periods relative to baseline.
20 weeks
The difference between EPX-100 vs placebo in proportion of participants with >50% reduction in the mean CCSF in the T+M periods relative to baseline.
Time Frame: 20 weeks
The difference between EPX-100 vs placebo in proportion of participants with >50% reduction in the mean CCSF in the T+M periods relative to baseline.
20 weeks
The total change in Seizure Severity using Hague Seizure Severity Scale (HASS).
Time Frame: 20 weeks
The total change in Seizure Severity using Hague Seizure Severity Scale (HASS).
20 weeks
The improvement in Clinical Global Impression (CGI).
Time Frame: 20 weeks
The improvement in Clinical Global Impression (CGI).
20 weeks
The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55).
Time Frame: 20 weeks
The total change in Quality of Life in Childhood Epilepsy short form (QOLCE 55).
20 weeks
The difference between EPX-100 vs placebo in proportion of participants with >25% reduction in the mean CCSF in the T+M periods relative to baseline.
Time Frame: 20 weeks
The difference between EPX-100 vs placebo in proportion of participants with >25% reduction in the mean CCSF in the T+M periods relative to baseline.
20 weeks
The mean difference between EPX-100 vs placebo per 28-days in the percent change of all seizures in the T+M periods relative to the baseline.
Time Frame: 20 weeks
The mean difference between EPX-100 vs placebo per 28-days in the percent change of all seizures in the T+M periods relative to the baseline.
20 weeks
The change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline.
Time Frame: 20 weeks
The change in the number of episodes of status epilepticus, in the T+M periods relative to the baseline.
20 weeks
The incidence of rescue anti-epileptic drug (AED) use between EPX-100 and placebo, as measured by the number of days on rescue AEDs in the T+M periods relative to the baseline.
Time Frame: 20 weeks
The incidence of rescue anti-epileptic drug (AED) use between EPX-100 and placebo, as measured by the number of days on rescue AEDs in the T+M periods relative to the baseline.
20 weeks
The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55).
Time Frame: 20 weeks
The individual item changes in Quality of Life in Childhood Epilepsy short form (QOLCE 55).
20 weeks
The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS).
Time Frame: 20 weeks
The individual item changes in Seizure Severity using Hague Seizure Severity Scale (HASS).
20 weeks
The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit
Time Frame: 20 weeks
The change in the Sleep Disturbance Scale for Children (SDSC) between EPX-100 and placebo by each scheduled visit
20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Epygenix

Collaborators

Forest Hills Lab
Liberyx Therapeutics

Investigators

  • Study Director: Lorianne Masouka, MD, Epygenix Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2020

Primary Completion (Estimated)

December 19, 2024

Study Completion (Estimated)

December 19, 2024

Study Registration Dates

First Submitted

July 6, 2020

First Submitted That Met QC Criteria

July 6, 2020

First Posted (Actual)

July 8, 2020

Study Record Updates

Last Update Posted (Actual)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 20, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPX-100-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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